Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection

NCT02247414 | Completed Phase 4 DMC

• 1 other identifier: YZUC-002
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether Warfarin Anticoagulation are effective and safe in Prevention of Portal Vein Thrombosis in Liver Cirrhotic Patients after Laparoscopic Splenectomy and Azygoportal Disconnection for Portal Hypertension

Conditions

Cirrhosis; Hypertension; Status;Splenectomy; Venous Thrombosis

Keywords

Cirrhosis; Hypertension; venous thrombosis; Warfarin; Splenectomy; Azygoportal Disconnection; Laparoscopy

Outcome Measures

Primary Outcomes (1)

• Proportions of patients who will suffer PVT or spleno-mesenteric thrombosis between oral anticoagulant Warfarin with dipyridamole group and oral Aspirin with dipyridamole group during the study period of 3 year from randomization

  3 years

Secondary Outcomes (5)

• Proportions of patients who will show improvement in Child Pugh (>2 points)in both groups

  3 years

• Proportions of patients who will show improvement in Model for End Stage Liver Disease (MELD)(>4 points)in both groups

  3 years

• Proportions of patients who will show decrease in hepatic decompensation defined as development of ascites, PSE, portal hypertensive bleeding, jaundice, spontaneous bacterial peritonitis, or systemic infection

  3 years

• Proportions of patients who will suffer from hepatocellular carcinoma in both groups

  3 years

• Overall survival in both groups

  3 years

Study Arms (2)

Warfarin with dipyridamole

EXPERIMENTAL

From postoperative day 3, patients will receive dipyridamole 25mg tid for three months along with subcutaneous Low Molecular Weight Heparin Calcium injection for first five days and Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3. Intially the INR will be monitored twice weekly with gradual escalation of dose to achieve target INR. After achieving the target INR, this is to be repeated every 4 weeks. The Doppler Ultra Sonography screening will be done every 3 months to assess the occurrence of portal vein thrombus, but the medications will be continue for one year irrespective of the occurrence of portal vein thrombus.

Drug: Warfarin; Drug: Dipyridamole; Drug: Low Molecular Weight Heparin

Aspirin with dipyridamole

ACTIVE COMPARATOR

From postoperative day 3, patients will receive oral dipyridamole 25mg tid for three months along with subcutaneous injection of Low Molecular Weight Heparin (4100 IU) for first five days and Aspirin Enterie Ccoated Tablets 100mg qd for one year.

Drug: Dipyridamole; Drug: Aspirin; Drug: Low Molecular Weight Heparin

Interventions

Warfarin DRUG

From postoperative day 3, patients will receive oral Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3 for 1 year.

Also known as: Warfarin Sodium, Athrombine, COUMADIN, PANAWARFIN

Warfarin with dipyridamole

Dipyridamole DRUG

From postoperative day 3, patients will receive oral dipyridamole 25mg tid for three months.

Also known as: Gardoxin, Coribon, Curantyl, Dilaplus

Aspirin with dipyridamole; Warfarin with dipyridamole

Aspirin DRUG

From postoperative day 3, patients will receive oral Aspirin Enterie Ccoated Tablets 100mg qd for 1 year.

Also known as: Acenterine, Acetard, Acetophen

Aspirin with dipyridamole

Low Molecular Weight Heparin DRUG

From postoperative day 3, patients will receive subcutaneous injection of Low Molecular Weight Heparin (4100 IU) once daily for first five days.

Also known as: Fraxiparine

Aspirin with dipyridamole; Warfarin with dipyridamole

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A clinical, radiological or histologic diagnosis of cirrhosis of any etiology
• Splenomegaly with secondary hypersplenism
• Bleeding portal hypertension
• INo evidence of PVT or spleno-mesenteric thrombosis by ultrasound evaluation and angio-CT
• Informed consent to participate in the study

You may not qualify if:

• Hepatocellular carcinoma or any other malignancy
• Hypercoagulable state other than the liver disease related
• DRUGS- oral contraceptives, anticoagulation or anti-platelet drugs
• Base line INR \>2
• Child-Pugh grade C
• Recent peptic ulcer disease
• History of Hemorrhagic stroke
• Pregnancy
• Uncontrolled Hypertension
• Age\>75 yrs
• Human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• Yangzhou University: lead

Study Sites (1)

Clinical Medical College of Yangzhou University

Yangzhou, Jiangsu, 225001, China

Location

Related Publications (2)

• Wu LF, Bai DS, Shi L, Jin SJ, Zhou BH, Jiang GQ. Predictors of portal vein thrombosis after laparoscopic splenectomy and azygoportal disconnection in hepatitis B cirrhosis: a prospective study. Surg Endosc. 2022 Jun;36(6):4090-4098. doi: 10.1007/s00464-021-08730-5. Epub 2021 Sep 13.

  PMID: 34518951 DERIVED

• Bai DS, Zhou BH, Qian JJ, Zhang C, Jin SJ, Jiang GQ. Effects of laparoscopic splenectomy and azygoportal disconnection on liver synthesis function and cirrhosis: a 2-year prospective study. Surg Endosc. 2020 Nov;34(11):5074-5082. doi: 10.1007/s00464-019-07307-7. Epub 2019 Dec 9.

  PMID: 31820157 DERIVED

MeSH Terms

Conditions

Fibrosis; Hypertension; Venous Thrombosis

Interventions

Warfarin; Dipyridamole; Aspirin; aspirin, magnesium oxide combination; Heparin, Low-Molecular-Weight; Nadroparin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrimidines; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Dou-Sheng Bai, MD

  Clinical Medical College of Yangzhou University

  STUDY CHAIR

• Guo-Qing Jiang, MS

  Clinical Medical College of Yangzhou University

  STUDY DIRECTOR

• Ping Chen, MD

  Clinical Medical College of Yangzhou University

  PRINCIPAL INVESTIGATOR

• Sheng-Jie Jin, MS

  Clinical Medical College of Yangzhou University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Master

Study Record Dates

• First Submitted: September 18, 2014
• First Posted: September 25, 2014
• Study Start: September 1, 2014
• Primary Completion: September 1, 2017
• Study Completion: April 1, 2018
• Last Updated: March 29, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)